SCIEX Debuts Breakthrough Method for Gene Therapies

Robust high-resolution determination of full, partial and empty capsid ratios for adeno-associated virus analysis

Framingham, MA — SCIEX a global leader in life science analytical technologies, launched an exciting new method for streamlining and improving the production of gene therapies. This innovative capillary electrophoretic method addresses a key customer challenge by analyzing AAVs to determine whether the therapeutic transgene payload has been successfully incorporated into the AAV vector product.

During the manufacturing of AAV vectors, capsids containing the full payload of transgenes are produced along with a high percentage of capsids that might not incorporate any of the transgenes (empty), or contain fragments of the transgene (partial). The presence of these impurities could increase immunogenicity or inhibit transduction of full capsids by competing for vector binding sites on cells.

“Successful incorporation of the transgene is critical for the efficacy and safety of gene therapies,” said Mani Krishnan, Vice President of Global Biopharma and Capillary Electrophoresis at SCIEX. “The ability to quickly determine capsid payload using small sample amounts will help drug developers speed their time to market, as well as deliver a safe and effective product.”

This new analytical method is able to detect with great precision whether the AAV capsids are full, partially full or empty. Key attributes include:

• A platform method that can be optimized for the separation of full, empty and partial capsids in AAV samples across multiple serotypes
• High resolving power: separating full and empty AAVs with very small isoelectric point (pI) differences of ≤ 0.1 pH unit
• Rapid analysis time: less than 1 hour per sample

“For gene therapy developers, time to market is critical. Unlike other classes of drugs, where a disease can be treated by multiple medications, gene therapeutics cure diseases by targeting specific genes. The one who gets there first wins. There is no second place,” says Rachel Legmann, PhD, Director, Technical Consultancy - Gene Therapy and Viral Vectors at Pall Biotech and SCIEX research partner. “That’s why scientists in biopharma are driven to develop a robust manufacturing process. But there’s a lack of reliable and reproducible methods to consistently produce AAV-based gene therapies, which means there is a lot of risk to get these therapies to market.”

“This new method offers a key to improving and streamlining the development and production process for AAV-based therapeutics,” continued Dr. Legmann. “When you have the right analytics for the entire in-process samples as well as release testing, you can navigate the upstream and downstream process to develop better quality and safer products – helping to reduce the cost of the manufacture.”